Tapping into our blood: Age-gender associated protein in human blood plasma and its potential relevance in skin aging
Podium 46
Presented by: Florence Florence
Introduction
Blood flows through every tissue in the human body. For this very reason, it is an excellent biofluid for identification of biomarkers to exploration of causative agent for different chronic diseases and aging phenotype, universally and/or gender-specific. Recent studies on human blood plasma proteome has revealed changes in protein profile across healthy human lifespan. Interestingly, some of the plasma proteins are reported to show notable difference in age dynamics between male and female. Despite skin’s extensive microcirculation, how changes in circulating plasma protein influence our skin are still not well studied. We hypothesized that the blood plasma protein dynamics may contribute to skin aging process, which may shed new light on skin intrinsic aging factor.
Aim
To identify candidate blood proteins that changes according to both age and gender as potential intrinsic factor in skin aging, as well as to evaluate its biological effects in normal human cultured fibroblasts and keratinocytes.
Methods
3K SOMAscan proteomics measurements from 3,301 human plasma samples (1,685 males and 1,616 females) of INTERVAL cohort (Cambridge, UK) were used for this study, with age ranged from 18 to 76 years and a median age of 45 years. Male and female data were analyzed separately. The data were clustered on similarity of their expression profile across age and the protein cluster that shows increase in detection level with age in female—but not in male—was isolated. Proteins were then selected based on their potential association with skin and was evaluated in cultured fibroblasts and keratinocytes.
Results
We found a cluster of 8 plasma proteins which detection across age increases differently in female compared to male. Among these proteins, Osteomodulin (OMD) was selected for further evaluation due to its previous report on possible interaction with collagen I, which is abundant in dermal skin. To confirm the potential effect of OMD to skin, we first evaluated OMD on cultured fibroblasts. Collagen I immunostaining result showed the disruption of collagen I in cultured fibroblast upon addition of OMD 1 μM and above. Quantitative ELISA also showed that collagen 1 secretion was suppressed in presence of high concentration of OMD. Furthermore, scanning electron microscopy (SEM) images demonstrated narrower distribution range of extracellular matrix fibril width in presence of OMD compared with control. On the top of that, addition of OMD to cultured keratinocytes also exhibited slow epidermal proliferation and significant decrease in relative expression of tight junction protein Occludin (OCLN).
Discussions
This study describes for the first time the potential biological effect of female-age associated plasma protein, Osteomodulin (OMD) on skin. From the result, OMD showed its potential contribution to skin aging due to action on fibroblast collagen I, keratinocytes proliferation, and tight junction. Inhibiting OMD activity in skin may be a potential new approach to tackle aging skin. Future studies on in vitro 3D skin model and human studies is needed to clarify aging phenotype which is potentially influenced by OMD.
Blood flows through every tissue in the human body. For this very reason, it is an excellent biofluid for identification of biomarkers to exploration of causative agent for different chronic diseases and aging phenotype, universally and/or gender-specific. Recent studies on human blood plasma proteome has revealed changes in protein profile across healthy human lifespan. Interestingly, some of the plasma proteins are reported to show notable difference in age dynamics between male and female. Despite skin’s extensive microcirculation, how changes in circulating plasma protein influence our skin are still not well studied. We hypothesized that the blood plasma protein dynamics may contribute to skin aging process, which may shed new light on skin intrinsic aging factor.
Aim
To identify candidate blood proteins that changes according to both age and gender as potential intrinsic factor in skin aging, as well as to evaluate its biological effects in normal human cultured fibroblasts and keratinocytes.
Methods
3K SOMAscan proteomics measurements from 3,301 human plasma samples (1,685 males and 1,616 females) of INTERVAL cohort (Cambridge, UK) were used for this study, with age ranged from 18 to 76 years and a median age of 45 years. Male and female data were analyzed separately. The data were clustered on similarity of their expression profile across age and the protein cluster that shows increase in detection level with age in female—but not in male—was isolated. Proteins were then selected based on their potential association with skin and was evaluated in cultured fibroblasts and keratinocytes.
Results
We found a cluster of 8 plasma proteins which detection across age increases differently in female compared to male. Among these proteins, Osteomodulin (OMD) was selected for further evaluation due to its previous report on possible interaction with collagen I, which is abundant in dermal skin. To confirm the potential effect of OMD to skin, we first evaluated OMD on cultured fibroblasts. Collagen I immunostaining result showed the disruption of collagen I in cultured fibroblast upon addition of OMD 1 μM and above. Quantitative ELISA also showed that collagen 1 secretion was suppressed in presence of high concentration of OMD. Furthermore, scanning electron microscopy (SEM) images demonstrated narrower distribution range of extracellular matrix fibril width in presence of OMD compared with control. On the top of that, addition of OMD to cultured keratinocytes also exhibited slow epidermal proliferation and significant decrease in relative expression of tight junction protein Occludin (OCLN).
Discussions
This study describes for the first time the potential biological effect of female-age associated plasma protein, Osteomodulin (OMD) on skin. From the result, OMD showed its potential contribution to skin aging due to action on fibroblast collagen I, keratinocytes proliferation, and tight junction. Inhibiting OMD activity in skin may be a potential new approach to tackle aging skin. Future studies on in vitro 3D skin model and human studies is needed to clarify aging phenotype which is potentially influenced by OMD.